Effects Of Broad-spectrum Antibiotic Administration And Germ-free Status On Biochemical And Endurance Adaptations To Regular Exercise In Mouse Muscle Tissue

Abstract

PURPOSE: The gut microbiota modulates a variety of physiologic processes. Recent studies from our group have shown that regular endurance exercise alters the composition of the gut microbiome and metabolome in mice and humans, and we hypothesized that the presence of microbes would affect endurance training adaptations in muscular endurance capacity, mitochondrial activity and gene expression in mice. METHODS: To discern differences in adaptations from 6 wks of voluntary wheel running (VWR), we depleted microbes with antibiotics (ABX) and used germ free (GF) mice to compare to control (CON). Male and female C57Bl/6 mice of all groups underwent daily VWR or sedentary (SED) conditions in a 2 x 3 design (VWR/SED, CON/ABX/GF, n = 56). After the intervention, treadmill endurance was assessed and gastrocnemius and soleus tissue were harvested and analyzed for activity of key Krebs cycle enzyme Citrate Synthase (CS) and expression of genes indicating mitochondrial adaptations respectively. RESULTS: Two way ANOVA revealed that VWR increased treadmill endurance, ABX had no effect, and that GF status significantly reduced performance. Additionally, VWR increased Citrate Synthase enzyme activity in gastrocnemius muscle tissue in all groups, and ABX and GF status did not reduce VWR’s effect or have an effect of their own. VWR also tended to increase expression of genes associated with increased mitochondrial activity (PGC-1α, CS, Succinate Dehydrogenase) in soleus tissue, but ABX had no effect on these observations. CONCLUSIONS: We conclude that ABX treatment and GF status do not affect VWR induced adaptations in endurance capacity, gastrocnemius mitochondrial activity or expression of metabolic genes in soleus tissue, but that GF status significantly hinders endurance capacity. This indicates that removing gut microbes does not inhibit muscular endurance training adaptations, but that germ free mice possess hindered endurance exercise capacity.